A2 Review article, Literature review, Systematic review
Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes : an EHTG, PLSD position statement (2023)

Møller, P., Seppälä, T. T., Ahadova, A., Crosbie, E. J., Holinski-Feder, E., Scott, R., Haupt, S., Möslein, G., Winship, I., Bajwa-ten Broeke, S. W., Kohut, K. E., Ryan, N., Bauerfeind, P., Thomas, L. E., Evans, D. G., Aretz, S., Sijmons, R. H., Half, E., Heinimann, K., . . . Dominguez-Valentin, M. (2023). Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes : an EHTG, PLSD position statement. Hereditary Cancer in Clinical Practice, 21, Article 19. https://doi.org/10.1186/s13053-023-00263-3

JYU authors or editors

Publication details

All authors or editors: Møller, Pal; Seppälä, Toni T.; Ahadova, Aysel; Crosbie, Emma J.; Holinski-Feder, Elke; Scott, Rodney; Haupt, Saskia; Möslein, Gabriela; Winship, Ingrid; Bajwa-ten Broeke, Sanne W.; et al.

Journal or series: Hereditary Cancer in Clinical Practice

ISSN: 1731-2302

eISSN: 1897-4287

Publication year: 2023

Publication date: 11/10/2023

Volume: 21

Article number: 19

Publisher: Biomed Central

Publication country: United Kingdom

Publication language: English

DOI: https://doi.org/10.1186/s13053-023-00263-3

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/90005

Additional information: On behalf of the Prospective Lynch Syndrome Database (www.plsd.eu) and The European Hereditary Tumour Group (www.ehtg.org)

Abstract

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an “average sex “or a pathogenic variant in an “average Lynch syndrome gene” and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host’s adaptive immune system’s ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system’s capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer.

Keywords: cancerous diseases; bowel cancer; hereditary diseases; epidemiology; oncogenes; clinical guidelines

Contributing organizations

Ministry reporting: Yes

VIRTA submission year: 2023

JUFO rating: 1